The objectives of this project are to understand the control of gene transcription during sporulation in Bacillus subtilis and how the expression of sporulation genes both directs, and is kept in register with, the course of morphogenesis. Sporulation involves the formation of a polar septum, which divides the developing cell into a forespore and a mother cell. Initially, the two cells lie side-by-side but later the forespore is engulfed by the mother cell. Evidence indicates that the polar septum is an organelle that is intimately involved in the establishment of cell-specific gene transcription. Differential transcription is governed initially by the action of transcription factor sigmaF in the forespore and sigmaE in the mother cell. After engulfment, sigmaF and sigmaE are replaced by sigmaG and sigmaK, respectively. Experiments will be carried out to understand how septum formation switches from a medial to a polar position. A pathway is known that links the activation of sigmaF to the polar septum. Experiments will be carried out to understand the roles of a septum-associated phosphatase and the proteolysis of an antisigma factor in the activation of sigmaF. The sigmaE factor is derived from pro-sigmaE, which associates with the septum prior to undergoing activation by proteolytic processing. Experiments will be carried out to understand the role of a septum-associated protein in restricting sigmaE to the mother cell. The sigmaK factor is derived from pro-sigmaK, whose activation is governed by an intercellular pathway that is coupled to the action of sigmaG. Experiments will be carried out to determine how the components of the pathway mediate pro-sigmaK processing in response to a signal from the forespore. Spore formation involves the assembly around the forespore of a morphogenetic protein that is produced under the control of sigmaE. Experiments will be carried out to understand the localization of this protein and its role in recruiting coat proteins and triggering cortex synthesis. These objectives address basic questions of differentiation and morphogenesis that are common to developing systems of many kinds, including complex systems of normal and abnormal development in higher organisms.